CA2668731A1

CA2668731A1 - Kinase inhibitors and methods for using the same

Kinase inhibitors and methods for using the same Download PDF

Info

Publication number: CA2668731A1
Authority: CA; Canada
Prior art keywords: 6alkyl; methyl; compound; optionally substituted; aryl
Prior art date: 2006-11-09
Legal status : Abandoned

Application number

CA002668731A

Other languages

English (en)

French (fr)

Inventor

Tobias Gabriel

Kin-Chun Thomas Luk

Joel Mcintosh

Current Assignee

F Hoffmann La Roche AG

Original Assignee

Individual

Priority date

2006-11-09

Filing date

2007-10-31

Publication date

2008-05-15

2007-10-31 Application filed by Individual filed Critical Individual

2008-05-15 Publication of CA2668731A1 publication Critical patent/CA2668731A1/en

Status Abandoned legal-status Critical Current

Links

238000000034 method Methods 0.000 title abstract description 57
229940043355 kinase inhibitor Drugs 0.000 title description 3
239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 147
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 50
201000010099 disease Diseases 0.000 claims abstract description 36
238000011282 treatment Methods 0.000 claims abstract description 32
-1 tetrahydropyran-4-yl Chemical group 0.000 claims description 277
239000001257 hydrogen Substances 0.000 claims description 54
229910052739 hydrogen Inorganic materials 0.000 claims description 54
239000000203 mixture Substances 0.000 claims description 48
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
150000002431 hydrogen Chemical class 0.000 claims description 30
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 27
125000000753 cycloalkyl group Chemical group 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 23
125000001072 heteroaryl group Chemical group 0.000 claims description 22
125000003118 aryl group Chemical group 0.000 claims description 21
125000002883 imidazolyl group Chemical group 0.000 claims description 21
125000001715 oxadiazolyl group Chemical group 0.000 claims description 21
125000000842 isoxazolyl group Chemical group 0.000 claims description 20
238000002360 preparation method Methods 0.000 claims description 20
125000001425 triazolyl group Chemical group 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
125000000623 heterocyclic group Chemical group 0.000 claims description 18
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
208000035475 disorder Diseases 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 7
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
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239000000546 pharmaceutical excipient Substances 0.000 claims description 7
125000000335 thiazolyl group Chemical group 0.000 claims description 7
201000004681 Psoriasis Diseases 0.000 claims description 6
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
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201000001320 Atherosclerosis Diseases 0.000 claims description 5
230000033115 angiogenesis Effects 0.000 claims description 5
125000003386 piperidinyl group Chemical group 0.000 claims description 5
230000002062 proliferating effect Effects 0.000 claims description 5
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206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
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125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 4
201000001441 melanoma Diseases 0.000 claims description 4
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208000037803 restenosis Diseases 0.000 claims description 4
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 4
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 3
208000031737 Tissue Adhesions Diseases 0.000 claims description 3
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125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 5
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230000001404 mediated effect Effects 0.000 abstract description 11
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108010077182 raf Kinases Proteins 0.000 abstract description 4
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239000000243 solution Substances 0.000 description 43
239000011541 reaction mixture Substances 0.000 description 31
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238000003556 assay Methods 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
230000002829 reductive effect Effects 0.000 description 24
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
239000004480 active ingredient Substances 0.000 description 16
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125000005843 halogen group Chemical group 0.000 description 14
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125000002947 alkylene group Chemical group 0.000 description 12
238000002868 homogeneous time resolved fluorescence Methods 0.000 description 12
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125000003545 alkoxy group Chemical group 0.000 description 11
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238000004519 manufacturing process Methods 0.000 description 11
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 11
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